rs960531

Positions:

• chr11-83965543-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142699.3(DLG2):​c.1057-75G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,217,834 control chromosomes in the GnomAD database, including 10,967 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.098 (940 hom., cov: 32)
  • Exomes 𝑓: 0.13 (10027 hom.)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

DLG2 (HGNC:2901): (discs large MAGUK scaffold protein 2) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. The encoded protein forms a heterodimer with a related family member that may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. Additional transcript variants have been described, but their full-length nature is not known. [provided by RefSeq, Dec 2008]

DLG2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.1057-75G>C		intron_variant		ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.1057-75G>C		intron_variant		1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.0979 AC: 14857 AN: 151754 Hom.: 943 Cov.: 32

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0933

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.0879

GnomAD4 exome AF: 0.129 AC: 137510 AN: 1065962 Hom.: 10027 AF XY: 0.129 AC XY: 69621 AN XY: 538112

Gnomad4 AFR exome AF: 0.0189

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.0983

Gnomad4 EAS exome AF: 0.0117

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.0762

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.0978 AC: 14860 AN: 151872 Hom.: 940 Cov.: 32 AF XY: 0.0963 AC XY: 7151 AN XY: 74254

Gnomad4 AFR AF: 0.0269

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.0933

Gnomad4 EAS AF: 0.0217

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0689

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.0879

Alfa AF: 0.123 Hom.: 166

Bravo AF: 0.0981

Asia WGS AF: 0.0880 AC: 306 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.68
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs960531; hg19: chr11-83676586; COSMIC: COSV54639566;